4/18/12

Page 1

MDUFA Performance Goals and Procedures ................................................................ 3

I. Process Improvements.......................................................................................... 3
A. Pre-Submissions .................................................................................................... 3
B. Submission Acceptance Criteria.......................................................................... 4
C. Interactive Review ................................................................................................ 5
D. Guidance Document Development ...................................................................... 5
E. Third Party Review............................................................................................... 5
F. Patient Safety and Risk Tolerance ...................................................................... 6
G. Low Risk Medical Device Exemptions ................................................................ 6
H. Emerging Diagnostics ........................................................................................... 6
II. Review Performance Goals - Fiscal Years 2013 Through 2017 As Applied to
Receipt Cohorts..................................................................................................... 6
A. Original Premarket Approval (PMA), Panel-Track Supplements, and
Premarket Report Applications........................................................................... 6
B. 180-Day PMA Supplements ................................................................................. 8
C. Real-Time PMA Supplements ............................................................................. 8
D. 510(k) Submissions................................................................................................ 8
E. Clinical Laboratory Improvement Amendments (CLIA) Waiver by
Application........................................................................................................... 10
F. Original Biologics Licensing Applications (BLAs) .......................................... 10
G. BLA Efficacy Supplements ................................................................................ 10
H. Original BLA and BLA Efficacy Supplement Resubmissions........................ 10
I. BLA Manufacturing Supplements Requiring Prior Approval....................... 11
III. Shared Outcome Goals ....................................................................................... 11
A. PMA ..................................................................................................................... 11
B. 510(k).................................................................................................................... 11
IV. Infrastructure...................................................................................................... 12
A. Scientific and Regulatory Review Capacity ..................................................... 12
B. Training ............................................................................................................... 12
C. Tracking System.................................................................................................. 12
V. Independent Assessment of Review Process Management ............................. 12
VI. Performance Reports.......................................................................................... 13
VII. Discretionary Waiver.......................................................................................... 16
VIII. Definitions and Explanations of Terms ............................................................ 16
A. Applicant.............................................................................................................. 16
B. Electronic Copy (e-Copy) ................................................................................... 16
C. FDA Days............................................................................................................. 16
D. MDUFA Decisions............................................................................................... 16
E. Pre-Submission.................................................................................................... 17
F. Substantive Interaction ...................................................................................... 18
G. Total Time to Decision........................................................................................ 18
H. BLA-related Definitions ..................................................................................... 19
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MDUFA Performance Goals and Procedures

The performance goals and procedures agreed to by the Center for Devices and
Radiological Health (CDRH) and the Center for Biologics Evaluation and Research
(CBER) of the United States Food and Drug Administration (“FDA” or “the Agency”)
for the medical device user fee program in the Medical Device User Fee Amendments of
2012, are summarized below.

FDA and the industry are committed to protecting and promoting public health by
providing timely access to safe and effective medical devices. Nothing in this letter
precludes the Agency from protecting the public health by exercising its authority to
provide a reasonable assurance of the safety and effectiveness of medical devices. Both
FDA and the industry are committed to the spirit and intent of the goals described in this
letter.

I. Process Improvements

A. Pre-Submissions

FDA will institute a structured process for managing Pre-Submissions. Pre-Submissions

subject to this process are defined in Section VIII, Definitions and Explanations of
Terms. The Agency will continue to improve the Pre-Submission process as resources
permit, but not to the detriment of meeting the quantitative review timelines and statutory
obligations. FDA will issue a draft guidance document and final guidance document on
Pre-Submissions.

Upon receipt of a Pre-Submission that requests feedback through a meeting or

teleconference, FDA intends to schedule the meeting or teleconference to occur within a
timely manner. In the Pre-Submission, the applicant will provide at least three suggested
dates and times when the applicant is available to meet.

It is FDA’s intent that within 14 calendar days of receipt of a request for a meeting or
teleconference, FDA will determine if the request meets the definition of a Pre-
Submission, and will inform the applicant if it does not meet the definition. FDA will
also determine if the request necessitates more than one meeting or teleconference. A
determination that the request does not meet the definition of a Pre-Submission will
require the concurrence of the branch chief and the reason for this determination will be
provided to the applicant. If the request meets the definition of a Pre-Submission, FDA
and the applicant will set a mutually agreeable time and date for the meeting.

At least 3 business days prior to the meeting, FDA will provide initial feedback to the
applicant by email, which will include: written responses to the applicant’s questions;
FDA’s suggestions for additional topics for the meeting or teleconference, if applicable;
or, a combination of both. If all of the applicant’s questions are addressed through written
responses, to the applicant’s satisfaction, FDA and the applicant can agree that a meeting
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or teleconference is no longer necessary and the written responses provided by email will
be considered the final written feedback to the Pre-Submission.

Meetings and teleconferences related to Pre-Submission will generally be limited to 1

hour. A longer meeting or teleconference time can be scheduled by mutual agreement by
the applicant and FDA.

Applicants will be responsible for developing draft minutes for a Pre-Submission meeting
or teleconference, and provide the draft minutes via email to FDA within 15 calendar
days of the meeting. The minutes will summarize the meeting discussions and include
agreements and any action items. FDA will provide any edits to the draft minutes to the
applicant via email within a timely manner. These minutes will become final 15 calendar
days after the applicant receives FDA’s edits, unless the applicant indicates that there is a
disagreement with how a significant issue or action item has been documented. In this
case, within a timely manner, the applicant and FDA will conduct a teleconference to
discuss that issue with FDA. At the conclusion of that teleconference, within a timely
manner FDA will finalize the minutes either to reflect the resolution of the issue or note
that this issue remains a point of disagreement.

FDA intends that feedback the Agency provides in a Pre-Submission will not change,
provided that the information submitted in a future investigational device exemption
(IDE) or marketing application is consistent with that provided in the Pre-Submission and
that the data in the future submission do not raise any important new issues materially
affecting safety or effectiveness. Modifications to FDA’s feedback will be limited to
situations in which FDA concludes that the feedback does not adequately address
important new issues materially relevant to a determination of safety or effectiveness.
Such a determination will be supported by the appropriate management concurrence
consistent with applicable guidance and SOPs.

B. Submission Acceptance Criteria

To facilitate a more efficient and timely review process, FDA will implement revised
submission acceptance criteria. The Agency will publish guidance outlining electronic
copy of submissions (e-Copy) and objective criteria for revised “refuse to accept/refuse to
file” checklists. FDA will publish draft and final guidance prior to implementation.
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C. Interactive Review

The Agency will continue to incorporate an interactive review process to provide for, and
encourage, informal communication between FDA and applicants to facilitate timely
completion of the review process based on accurate and complete information.
Interactive review entails responsibilities for both FDA and applicants. As described in
the guidance document, Interactive Review for Medical Device Submissions: 510(k)s,
Original [Premarket Approvals] PMAs, PMA Supplements, Original BLAs, and BLA
Supplements, both FDA and industry believe that an interactive review process for these
types of premarket medical device submissions should help facilitate timely completion
of the review based on accurate and complete information. Interactive review is intended
to facilitate the efficient and timely review and evaluation by FDA of premarket
submissions. The interactive review process contemplates increased informal interaction
between FDA and applicants, including the exchange of scientific and regulatory
information.

D. Guidance Document Development

FDA will apply user fee revenues to supplement the improvement of the process of
developing, reviewing, tracking, issuing, and updating guidance documents. The Agency
will continue to develop guidance documents and improve the Guidance Development
process as resources permit, but not to the detriment of meeting the quantitative review
timelines and statutory obligations.

FDA will update its website in a timely manner to reflect the following:
1. The Agency’s review of previously published device guidance documents,
including the deletion of guidance documents that no longer represent the
Agency’s interpretation of, or policy on, a regulatory issue, and notation of
guidance documents that are under review by the Agency;
2. A list of prioritized device guidance documents (an “A-list”) that the Agency
intends to publish within 12 months of the date this list is published each fiscal
year; and
3. A list of device guidance documents (a “B-list”) that the Agency intends to
publish, as the Agency’s guidance-development resources permit each fiscal year.

The Agency will establish a process allowing stakeholders an opportunity to:

1. Provide meaningful comments and/or propose draft language for proposed
guidance topics in the “A” and “B” lists.
2. Provide suggestions for new or different guidance documents; and
3. Comment on the relative priority of topics for guidance.

E. Third Party Review

The Agency will continue to support the third party review program and agrees to work
with interested parties to strengthen and improve the current program while also
establishing new procedures to improve transparency. The Agency will continue to
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improve the third party review program as resources permit, but not to the detriment of
meeting the quantitative review timelines and statutory obligations.

F. Patient Safety and Risk Tolerance

FDA will fully implement final guidance on the factors to consider when making benefit-
risk determinations in medical device premarket review. This guidance will focus on
factors to consider in the premarket review process, including patient tolerance for risk,
magnitude of the benefit, and the availability of other treatments or diagnostic tests.

Over the period of MDUFA III, FDA will meet with patient groups to better understand
and characterize the patient perspective on disease severity or unmet medical need.

In addition, FDA will increase its utilization of FDA’s Patient Representatives as Special
Government Employee consultants to CDRH to provide patients’ views early in the
medical product development process and ensure those perspectives are considered in
regulatory discussions. Applicable procedures governing conflicts of interest and
confidentiality of proprietary information will be utilized for these consultations.

G. Low Risk Medical Device Exemptions

By the end of FY 2013, FDA will propose additional low risk medical devices to exempt
from premarket notification. Within two years of such proposal, FDA intends to issue a
final rule exempting additional low risk medical devices from premarket notification.

H. Emerging Diagnostics

FDA will work with industry to develop a transitional In Vitro Diagnostics (IVD)
approach for the regulation of emerging diagnostics.

II. Review Performance Goals - Fiscal Years 2013 Through 2017 As Applied to
Receipt Cohorts

The overall objective of the review performance goals stated herein is to assure more
timely access to safe and effective medical devices.

A. Original Premarket Approval (PMA), Panel-Track Supplements, and

Premarket Report Applications

The performance goals in this section apply to all Original Premarket Approval, Panel-
Track Supplements, and Premarket Report Applications, including those that are accepted
for priority review (previously referred to as expedited).

FDA will communicate with the applicant regarding whether the application has been
accepted for filing review within 15 calendar days of receipt of the application. This
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communication consists of a fax, email, or other written communication that a) identifies
the reviewer assigned to the submission, and b) acknowledges acceptance/rejection of the
submission based upon the review of the submission against objective acceptance criteria
outlined in a published guidance document.

If the application is not accepted for filing review, FDA will notify the applicant of those
items necessary for the application to be considered accepted for filing review.

For those applications that are accepted for filing review, FDA will communicate the
filing status within 45 calendar days of receipt of the application.

For those applications that are not filed, FDA will communicate to the applicant the
specific reasons for rejection and the information necessary for filing.

If the application is filed, FDA will communicate with the applicant through a
Substantive Interaction within 90 calendar days of the filing date of the application for:
65% of submissions received in FY 2013; 75% of submissions received in FY 2014; 85%
of submissions received in FY 2015; and 95% of submissions received in FY 2016
through FY 2017.

When FDA issues a major deficiency letter, that letter will be based upon a complete
review of the application and will include all deficiencies. Any subsequent deficiencies
will be limited to issues raised by the information provided by the applicant in its
response, unless FDA concludes that the initial deficiencies identified do not adequately
address important new issues materially relevant to a determination of safety or
effectiveness. Such a determination will be supported by the appropriate management
concurrence consistent with applicable guidance and SOPs. Issues related to post-
approval studies, if applicable, and revisions to draft labeling will typically be addressed
through interactive review once major deficiencies have been adequately addressed.

For submissions that do not require Advisory Committee input, FDA will issue a
MDUFA decision within 180 FDA Days for: 70% of submissions received in FY 2013;
80% of submissions received in FY 2014 and FY 2015; and 90% of submissions received
in FY 2016 and FY 2017.

For submissions that require Advisory Committee input, FDA will issue a MDUFA
decision within 320 FDA Days for: 50% of submissions received in FY 2013; 70% of
submissions received in FY 2014; 80% of submissions received in FY 2015 and FY
2016; and 90% of submissions received in FY 2017.

If in any one fiscal year, the number of submissions that require Advisory Committee
input is less than 10, then it is acceptable to combine such submissions with the
submissions for the following year(s) in order to form a cohort of 10 or more
submissions, upon which the combined years’ submissions will be subject to the
performance goal for the fiscal year in question. If the number of submissions that
require Advisory Committee input is less than 10 for FY 2017, it is acceptable to
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combine such submissions with the submissions in the prior year in order to form a
cohort of 10 or more submissions; in such cases, FDA will be held to the FY 2017
performance goal for the combined years’ submissions.

To facilitate an efficient review prior to the Substantive Interaction, and to incentivize

submission of a complete application, submission of an unsolicited major amendment
prior to the Substantive Interaction extends the FDA Day review clock by the number of
FDA Days that have elapsed. Submission of an unsolicited major amendment after the
Substantive Interaction extends the FDA Day goal by the number of FDA Days equal to
75% of the difference between the filing date and the date of receipt of the amendment.

For all PMA submissions that do not reach a MDUFA decision by 20 days after the
applicable FDA Day goal, FDA will provide written feedback to the applicant to be
discussed in a meeting or teleconference, including all outstanding issues with the
application preventing FDA from reaching a decision. The information provided will
reflect appropriate management input and approval, and will include action items for
FDA and/or the applicant, as appropriate, with an estimated date of completion for each
party to complete their respective tasks. Issues should be resolved through interactive
review. If all of the outstanding issues are adequately presented through written
correspondence, FDA and the applicant can agree that a meeting or teleconference is not
necessary.

In addition, information about submissions that miss the FDA Day goal will be provided
as part of FDA’s Performance Reports, as described in Section VI.

B. 180-Day PMA Supplements

FDA will communicate with the applicant through a Substantive Interaction within 90
calendar days of receipt of the submission for: 65% of submissions received in FY 2013;
75% of submissions received in FY 2014; 85% of submissions received in FY 2015; and
95% of submissions received in FY 2016 through FY 2017.

FDA will issue a MDUFA decision within 180 FDA Days for: 85% of submissions
received in FY 2013; 90% of submissions received in FY 2014 and FY 2015; and 95% of
submissions received in FY 2016 through FY 2017.

C. Real-Time PMA Supplements

FDA will issue a MDUFA decision within 90 FDA Days for: 90% of submissions
received in FY 2013 and FY 2014; and 95% of submissions received in FY 2015 through
FY 2017.

D. 510(k) Submissions
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FDA will communicate with the applicant regarding whether the submission has been
accepted for review within 15 calendar days of receipt of the submission. For those
submissions that are not accepted for review, FDA will notify the applicant of those items
necessary for the submission to be considered accepted.

This communication includes a fax, email, or other written communication that a)

identifies the reviewer assigned to the submission, and b) acknowledges
acceptance/rejection of the submission based upon the review of the submission against
objective acceptance criteria outlined in a published guidance document. This
communication represents a preliminary review of the submission and is not indicative of
deficiencies that may be identified later in the review cycle.

FDA will communicate with the applicant through a Substantive Interaction within 60
calendar days of receipt of the submission for: 65% of submissions received in FY 2013;
75% of submissions received in FY 2014; 85% of submissions received in FY 2015; and
95% of submissions received in FY 2016 through FY 2017.

Deficiencies identified in a Substantive Interaction, such as a telephone/email hold or

Additional Information Letter, will be based upon a complete review of the submission
and will include all deficiencies. Any subsequent deficiencies will be limited to issues
raised by the information provided by the applicant in its response, unless FDA concludes
that the initial deficiencies identified do not adequately address important new issues
materially relevant to a determination of substantial equivalence. Such a determination
will be supported by the appropriate management concurrence consistent with applicable
guidance and SOPs.

For submissions received in FY 2013, FDA will issue a MDUFA decision for 91% of
510(k) submissions within 90 FDA Days.

For submissions received in FY 2014, FDA will issue a MDUFA decision for 93% of
510(k) submissions within 90 FDA Days.

For submissions received in FY 2015 through FY 2017, FDA will issue a MDUFA
decision for 95% of 510(k) submissions within 90 FDA Days.

For all 510(k) submissions that do not reach a MDUFA decision within 100 FDA Days,
FDA will provide written feedback to the applicant to be discussed in a meeting or
teleconference, including all outstanding issues with the application preventing FDA
from reaching a decision. The information provided will reflect appropriate management
input and approval, and will include action items for FDA and/or the applicant, as
appropriate, with an estimated date of completion for each party to complete their
respective tasks. Issues should be resolved through interactive review. If all of the
outstanding issues are adequately presented through written correspondence, FDA and
the applicant can agree that a meeting or teleconference is not necessary.
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In addition, information about submissions that miss the FDA Day goal will be provided
as part of FDA’s Performance Reports, as described in Section VI.

E. Clinical Laboratory Improvement Amendments (CLIA) Waiver by

Application

FDA will engage in a Substantive Interaction with the applicant within 90 days for 95%
of the applications.

During the pre-submission process, if the applicant informs FDA that it plans to submit a
dual submission (510(k) and CLIA Waiver application), FDA will issue a decision for
90% of such applications within 210 FDA days.

For “CLIA Waiver by application” submissions FDA will issue a MDUFA decision for
95% of the applications that do not require Advisory Committee input within 180 FDA
days.

For “CLIA Waiver by application” submissions FDA will issue a MDUFA decision for
95% of the applications that require Advisory Committee input within 330 FDA days.

To provide greater transparency, FDA will issue guidance regarding review and
management expectations throughout the entire submission process.

F. Original Biologics Licensing Applications (BLAs)

FDA will review and act on standard original BLA submissions within 10 months of
receipt for 90% of submissions.

FDA will review and act on priority original BLA submissions within 6 months of receipt
for 90% of submissions.

G. BLA Efficacy Supplements

FDA will review and act on standard BLA efficacy supplement submissions within 10
months of receipt for 90% of submissions.

FDA will review and act on priority BLA efficacy supplement submissions within 6
months of receipt for 90% of submissions.

H. Original BLA and BLA Efficacy Supplement Resubmissions

FDA will review and act on Class 1 original BLA and BLA efficacy supplement
resubmissions within 2 months of receipt for 90% of submissions.

FDA will review and act on Class 2 original BLA and BLA efficacy supplement
resubmissions within 6 months of receipt for 90% of submissions.
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I. BLA Manufacturing Supplements Requiring Prior Approval

FDA will review and act on BLA manufacturing supplements requiring prior approval
within 4 months of receipt for 90% of submissions.

III. Shared Outcome Goals

The program and initiatives outlined in this document are predicated on significant
interaction between the Agency and applicants. FDA and representatives of the medical
device industry agree that the process improvements outlined in this letter, when
implemented by all parties as intended, should reduce the average Total Time to Decision
for PMA applications and 510(k) submissions, provided that the total funding of the
device review program adheres to the assumptions underlying this agreement. FDA and
applicants share the responsibility for achieving this objective of reducing the average
Total Time to Decision, while maintaining standards for safety and effectiveness.
Success of this program will require the cooperation and dedicated efforts of FDA and
applicants to reduce their respective portions of the total time to decision.

FDA will be reporting total time performance quarterly as described in Section VI. FDA
and industry will participate in the independent assessment of progress toward this
outcome, as described in Section V above. As appropriate, key findings and
recommendations from this assessment will be implemented by FDA.

A. PMA

Beginning in Fiscal Year 2013, FDA will report on an annual basis the average Total
Time to Decision as defined in Section VIII.G for the three most recent closed receipt
cohorts. For submissions received beginning in Fiscal Year 2013, the average Total
Time to Decision goal for FDA and industry is 395 calendar days. For submissions
received beginning in Fiscal Year 2015, the average Total Time to Decision goal for
FDA and industry is 390 calendar days. For submissions received beginning in Fiscal
Year 2017, the average Total Time to Decision goal for FDA and industry is 385 calendar
days.

B. 510(k)

Beginning in Fiscal Year 2013, FDA will report on an annual basis the average Total
Time to Decision as defined in Section VIII.G for the most recent closed receipt cohort.
For submissions received beginning in Fiscal Year 2013, the average Total Time to
Decision goal for FDA and industry is 135 calendar days. For submissions received
beginning in FY 2015, the average Total Time to Decision goal for FDA and industry is
130 calendar days. For submissions received beginning in FY 2017, the average Total
Time to Decision goal for FDA and industry is 124 calendar days.
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IV. Infrastructure

A. Scientific and Regulatory Review Capacity

The Agency will apply user fee revenues to reduce the ratio of review staff to front line
supervisors in the Pre-Market review program and to enhance and supplement scientific
review capacity by hiring device application reviewers and leveraging external experts
needed to assist with the review of device applications.

The Agency will seek to obtain streamlined hiring authority for all MDUFA-related
positions prior to and during the MDUFA III period.

During MDUFA III, FDA will also work with industry to benchmark best practices for
retaining employees (both financial and non-financial).

B. Training

Prior to the commencement of MDUFA III, CDRH will implement its Reviewer
Certification Program. FDA commits to holding a minimum of two medical device
Vendor Days each year.

CDRH will apply user fee revenues to supplement the following training programs:

1) Management training for Branch Chiefs and Division Directors.

2) MDUFA III Training Program for all staff.
3) Reviewer Certification Program for new CDRH reviewers. FDA will publish
the curriculum of this program and other course offerings. FDA will consider
comments from stakeholders when making updates to courses and determining
course offerings.
4) Specialized training to provide continuous learning for all staff.

C. Tracking System

FDA will continue efforts to improve its IT systems with a future expectation of
facilitating availability of real-time status information for submissions.

V. Independent Assessment of Review Process Management

FDA and the device industry will participate in a comprehensive assessment of the
process for the review of device applications. The assessment will include consultation
with both FDA and industry. The assessment shall be conducted in two phases under
contract to FDA by a private, independent consulting firm capable of performing the
technical analysis, management assessment, and program evaluation tasks required to
address the assessment scope described below. For Phase 1, FDA will award the
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contract no later than the end of the second quarter of FY13. Findings on high-priority
recommendations (i.e., those likely to have a significant impact on review times) will be
published within six months of award; final comprehensive findings and
recommendations will be published within 1 year of contract award. FDA will publish an
implementation plan within 6 months of receipt of each set of recommendations. For
Phase 2 of the independent assessment, the contractor will evaluate the implementation of
recommendations and publish a written assessment no later than February 1, 2016.

The assessment will address FDA’s premarket review process using an assessment
framework that draws from appropriate quality system standards, including, but not
limited to, management responsibility, document controls and records management, and
corrective and preventive action.

The scope of the assessment will include, but not be limited to, the following areas:

1. Identification of process improvements and best practices for conducting

predictable, efficient, and consistent premarket reviews that meet regulatory
review standards.
2. Analysis of elements of the review process (including the Pre-Submission
process, IDE, 510(k) and PMA reviews) that consume or save time to facilitate a
more efficient process. This includes analysis of root causes for inefficiencies that
may affect review performance and total time to decision. This will also include
recommended actions to correct any failures to meet MDUFA goals. Analysis of
the review process will include the impact of combination products, companion
diagnostics products, and laboratory developed tests on the review process.
3. Assessment of FDA methods and controls for collecting and reporting
information on premarket review process resource use and performance.
4. Assessment of effectiveness of FDA’s Reviewer Training Program
implementation.
5. Recommendations for ongoing periodic assessments and any additional, more
detailed or focused assessments.

FDA will incorporate findings and recommendations, as appropriate, into its management
of the premarket review program. FDA will analyze the recommendations for
improvement opportunities identified in the assessment, develop and implement a
corrective action plan, and assure its effectiveness. FDA also will incorporate the results
of the assessment into a Good Review Management Practices (GRMP) guidance
document. FDA’s implementation of the GRMP guidance will include initial and
ongoing training of FDA staff, and periodic audits of compliance with the guidance.

VI. Performance Reports

The Agency will report its progress toward meeting the goals described in this letter, as
follows. If, throughout the course of MDUFA III, the Agency and Industry agree that a
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different format or different metrics would be more useful, the reporting will be modified
accordingly as per the agreement of both FDA and Industry.

1. Quarterly reporting at the CDRH Division level/CBER Center level (in recognition of
the significantly smaller number of submissions reviewed at CBER):
1.1. For 510(k) submissions, reporting will include:
i. Average and quintiles of the number of calendar days to Substantive
Interaction
ii. Average, and quintiles of the number of FDA Days, Industry Days, and
Total Days to a MDUFA decision
iii. Average number of review cycles.
iv. Rate of submissions not accepted for review
1.2. For PMA submissions, reporting will include:
i. Average and quintiles of the number of calendar days to Substantive
Interaction for Original PMA, Panel-Track PMA Supplement, and
Premarket Report Submissions
ii. Average and quintiles of the of FDA Days, Industry Days, and Total Days to
a MDUFA decision
iii. Rate of applications not accepted for filing review, and rate of applications
not filed
1.3. For Pre-Submissions, reporting will include:
i. Number of all qualified Pre-Submissions received
ii. Average and quintiles of the number of calendar days from submission to
meeting or teleconference (if necessary)
iii. Number of Pre-Submissions that require a meeting
1.4. For IDE applications, reporting will include:
i. Number of original IDEs received
ii. Average number of amendments prior to approval or conditional approval of
the IDE (this information will be provided beginning no later than the
quarter that starts 10/1/2013)

2. CDRH will report quarterly, and CBER will report annually, the following data at the
Center level:
2.1. Rate of NSE decisions for 510(k) submissions
2.2. Rate of withdrawals for 510(k) and PMA submissions
2.3. Rate of Not Approvable decisions for PMA submissions
2.4. Key product areas or other issues that FDA identifies as noteworthy because of a
potential effect on performance, including significant rates of Additional
Information requests
2.5. Specific topic or product area as it relates to performance goals, agreed upon at
the previous meeting
2.6. Number of submissions that missed the goals and the total number of elapsed
calendar days broken down into FDA days and industry days
2.7. Newly released draft and final guidance documents, and status of other priority
guidance documents
2.8. Agency level summary of fee collections
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2.9. Independent assessment implementation plan status
2.10. Results of independent assessment and subsequent periodic audits and
progress toward implementation of the recommendations and any corrective
action
2.11. Number of discretionary fee waivers or reductions granted by type of
submission

3. In addition, the Agency will provide the following information on an annual basis:
3.1. Qualitative and quantitative update on how funding is being used for the device
review process, including the percentage of review time devoted to direct review
of applications
3.2. How funding is being used to enhance scientific review capacity
3.3. The number of Premarket Report Submissions received
3.4. Summary information on training courses available to CDRH and CBER
employees, including new reviewers, regarding device review and the
percentage of applicable staff that have successfully completed each such
course. CDRH will provide information concerning any revisions to the new
reviewer training program curriculum.
3.5. Performance on the shared outcome goal for average Total Time to decision
3.6. For 510(k) submissions, reporting will include:
i. Number of submissions reviewed by a Third Party
ii. Number of Special Submissions
iii. Number of Traditional Submissions
iv. Average and number of days to Accept/Refuse to Accept
v. Number of Abbreviated Submissions
3.7. For PMA submissions, reporting will include the number of the following types
of PMA submissions received:
i. Original PMAs
ii. Priority PMAs
iii. Premarket Reports
iv. Panel-Track PMA Supplement
v. PMA Modules
vi. 180-Day PMA Supplements
vii. Real-Time PMA Supplements
3.8. For De Novo Classification Petitions, reporting will include:
i. Number of submissions received
ii. Average number of calendar days to a MDUFA decision
3.9. For CLIA waiver applications, reporting will include:
i. Number of CLIA waiver applications received
ii. Average and quintiles of the number of calendar days to Substantive
Interaction
iii. Average and quintiles of the number of FDA Days, Industry Days, and Total
Days to a MDUFA decision and a discussion of any trends in the data
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VII. Discretionary Waiver

The Agency will seek authority to grant discretionary fee waivers or reductions in the
interest of public health. Notwithstanding any fee waivers or reductions granted by the
Agency under this discretionary authority, FDA remains committed to meeting the goals
described in this letter. Any submission subject to a fee waiver or reduction under this
discretionary authority shall not be subject to the goals specified in this letter and shall be
reviewed by the Agency as resources permit. This discretionary authority will expire at
the end of MDUFA III.

VIII. Definitions and Explanations of Terms

A. Applicant

Applicant means a person who makes any of the following submissions to FDA:

· an application for premarket approval under section 515;

· a premarket notification under section 510(k);
· an application for investigational device exemption under section 520(g);
· a Pre-Submission;
· a CLIA waiver application.

B. Electronic Copy (e-Copy)

An electronic copy is an exact duplicate of a paper submission, created and submitted on

a CD, DVD, or in another electronic media format that FDA has agreed to accept,
accompanied by a copy of the signed cover letter and the complete original paper
submission. An electronic copy is not considered to be an electronic submission.

C. FDA Days

FDA Days are those calendar days when a submission is considered to be under review at
the Agency for submissions that have been accepted (510(k)) or filed (PMA). FDA Days
begin on the date of receipt of the submission or of the amendment to the submission that
enables the submission to be accepted (510(k)) or filed (PMA).

D. MDUFA Decisions

Original PMAs: Decisions for Original PMAs are Approval, Approvable, Approvable
Pending GMP Inspection, Not Approvable, Withdrawal, and Denial.

180-Day PMA Supplements: Decisions for 180-Day PMA Supplements include

Approval, Approvable, and Not Approvable.
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Real-Time PMA Supplements: Decisions for Real-Time PMA supplements include
Approval, Approvable, and not Approvable.

510(k)s: Decisions for 510(k)s are substantially equivalent (SE) or not substantially
equivalent (NSE).

Submissions placed on Application Integrity Program Hold will be removed from the
MDUFA cohort.

E. Pre-Submission

A Pre-Submission includes a formal written request from an applicant for feedback from
FDA which is provided in the form of a formal written response or, if the manufacturer
chooses, a meeting or teleconference in which the feedback is documented in meeting
minutes. A Pre-Submission meeting is a meeting or teleconference in which FDA
provides its substantive feedback on the Pre-Submission.

A Pre-Submission provides the opportunity for an applicant to obtain FDA feedback prior
to intended submission of an investigational device exemption or marketing application.
The request must include specific questions regarding review issues relevant to a planned
IDE or marketing application (e.g., questions regarding pre-clinical and clinical testing
protocols or data requirements). A Pre-Submission is appropriate when FDA’s feedback
on specific questions is necessary to guide product development and/or application
preparation.

The following forms of FDA feedback to applicants are not considered Pre-Submissions.
However, if the requested feedback meets the criteria for a Pre-Submission, outlined
above, FDA will contact the sponsor, and with the concurrence of the sponsor, may
convert the request to a Pre-Submission.

· General information requests initiated through the Division of Small

Manufacturers, International and Consumer Assistance (DSMICA)

· General questions regarding FDA policy or procedures

· Meetings or teleconferences that are intended to be informational only,

including, but not limited to, those intended to educate the review team on
new device(s) with significant differences in technology from currently
available devices, or to update FDA about ongoing or future product
development, without a request for FDA feedback on specific questions
related to a planned submission

· Requests for clarification on technical guidance documents, especially where

contact is recommended by FDA in the guidance document. However, the
following requests will generally need to be submitted as a Pre-Submission in
order to ensure appropriate input from multiple reviewers and management:
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recommendations for device types not specifically addressed in the guidance
document; recommendations for nonclinical or clinical studies not addressed
in the guidance document; requests to use an alternative means to address
recommendations specified in a guidance document.

· Phone calls or email messages to reviewers that can be readily answered based
on a reviewer’s experience and knowledge and do not require the involvement
of a broader number of FDA staff beyond the routine involvement of the
reviewer’s supervisor and more experienced mentors.

· Interactions requested by either the applicant or FDA during the review of a

marketing application (i.e., following submission of a marketing application,
but prior to reaching an FDA Decision).

F. Substantive Interaction

Substantive Interaction is an email, letter, teleconference, video conference, fax, or other

form of communication such as a request for Additional Information or Major Deficiency
letters by FDA notifying the applicant of substantive deficiencies identified in initial
submission review, or a communication stating that FDA has not identified any
deficiencies in the initial submission review and any further minor deficiencies will be
communicated through interactive review. An approval or clearance letter issued prior to
the Substantive Interaction goal date will qualify as a Substantive Interaction.

If substantive issues warranting issuance of an Additional Information or Major

Deficiency letter are not identified, interactive review should be used to resolve any
minor issues and facilitate an FDA decision. In addition, interactive review will be used,
where, in FDA’s estimation, it leads to a more efficient review process during the initial
review cycle (i.e., prior to a Substantive Interaction) to resolve minor issues such as
revisions to administrative items (e.g., 510(k) Summary/Statement, Indications for Use
statement, environmental impact assessment, financial disclosure statements); a more
detailed device description; omitted engineering drawings; revisions to labeling; or
clarification regarding nonclinical or clinical study methods or data.

Minor issues may still be included in an Additional Information or Major Deficiency

letter where related to the resolution of the substantive issues (e.g., modification of the
proposed Indications for Use may lead to revisions in labeling and administrative items),
or if they were still unresolved following interactive review attempts. Both interactive
review and Substantive Interactions will occur on the review clock except upon the
issuance of an Additional Information or Major Deficiency Letter which stops the review
clock.

G. Total Time to Decision

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Total Time to Decision is the number of calendar days from the date of receipt of an
accepted or filed submission to a MDUFA decision.

The average Total Time to Decision for 510(k) submissions is calculated as the trimmed
mean of Total Times to Decision for 510(k) submissions within a closed cohort,
excluding the highest 2% and the lowest 2% of values. A cohort is closed when 99% of
the accepted submissions have reached a decision.

The average Total Time to Decision for PMA applications is calculated as the three-year
rolling average of the annual Total Times to Decision for applications (for example, for
FY2015, the average Total Time to Decision for PMA applications would be the average
of FY2013 through FY2015) within a closed cohort, excluding the highest 5% and the
lowest 5% of values. A cohort is closed when 95% of the applications have reached a
decision.

H. BLA-related Definitions

Review and act on – the issuance of a complete action letter after the complete review of
a filed complete application. The action letter, if it is not an approval, will set forth in
detail the specific deficiencies and, where appropriate, the actions necessary to place the
application in condition for approval.

Class 1 resubmitted applications – applications resubmitted after a complete response

letter that includes the following items only (or combinations of these items):
(a) Final printed labeling
(b) Draft labeling
(c) Safety updates submitted in the same format, including tabulations, as the
original safety submission with new data and changes highlighted (except
when large amounts of new information including important new adverse
experiences not previously reported with the product are presented in the
resubmission)
(d) Stability updates to support provisional or final dating periods
(e) Commitments to perform Phase 4 studies, including proposals for such
studies
(f) Assay validation data
(g) Final release testing on the last 1-2 lots used to support approval
(h) A minor reanalysis of data previously submitted to the application
(determined by the Agency as fitting the Class 1 category)
(i) Other minor clarifying information (determined by the Agency as fitting
the Class 1 category)
(j) Other specific items may be added later as the Agency gains experience
with the scheme and will be communicated via guidance documents to
industry
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Class 2 resubmitted applications – resubmissions that include any other items,
including any item that would require presentation to an advisory committee